Diagnosis and

Management
o f Vul v a r U l c e r s
Grace D. Bandow, MDa,b

KEYWORDS
 Genital ulceration  Aphthae  Vulva  Ulcers
 Behçet’s disease  Crohn’s disease

ULCERS VERSUS EROSIONS common lesion affecting oral mucosa, occurring

Ulcers should be differentiated from erosions both
clinically and histologically. This is accomplished
on the basis of depth. An erosion is a defect in
the epidermis only, resulting in a red, smooth,
moist, superficial, atrophic plaque. Ulcers are
deeper, extending into the underlying dermis,
and appear necrotic at the base with either yellow,
fibrinous material or an eschar adherent to it.
Large, deep, or long-standing ulcers heal with
scarring, while erosions and superficial ulcers typi-
cally heal without scarring. Erosive diseases of the
vulva are reviewed elsewhere.
TYPES OF ULCERS
Causes of vulvar ulcers are diverse and can be
divided into infectious and noninfectious cate-
gories. Infectious causes include primary syphilis,
lymphogranuloma venereum (LGV), chancroid,
granuloma inguinale (GI), and herpes simplex virus
(HSV). In the United States, HSV is the most
common of these. Noninfectious ulcers include
those caused by drug reactions or adverse effects,
autoimmune or inflammatory disease, trauma, and
aphthous ulcers.
Aphthous Ulcers
Oral aphthae (aphthosis, aphthous stomatitis,
recurrent aphthous ulcers) have similar character-
istics to vulvar aphthae. Commonly known as
cancer sores, they are painful, recurring lesions
of the oral mucous membranes. This is the most
in up to 20% of the general population and 60%
of select groups.1e3 They are typically very tender
and can become painful enough to interfere with
speech, mastication, or swallowing.4
Both oral and vulvar aphthae have been classi-
fied into three groups: minor, major, and herpeti-
form.5 Minor aphthae are smaller than 1 cm and
heal within 7 to 10 days without scarring. Major
aphthae are greater than 1 cm, deep, extremely
painful, and heal with scarring in 10 to 30 days.
Herpetiform aphthae are multiple, grouped, small
ulcers that heal without scarring, and despite the
name, are not associated with HSV.
Aphthae are classified further based on clinical
course, as either simple or complex. Most patients
have simple aphthosis, or several episodes per
year of either minor, major, or herpetiform aphthae
separated by disease-free periods. Complex aph-
thosis is defined as either almost constant pres-
ence of three or more ulcers, or recurrent oral
and genital aphthae and exclusion of Behçet’s
disease (BD).6
Vulvar aphthae are thought to be relatively rare,
and they are reported infrequently. Clinicians who
specialize in caring for women and girls with vulvar
disease, however, believe that vulvar aphthae are,
in fact, not rare. Although studies looking at inci-
dence and characteristics of vulvar aphthae are
few, authors agree that most cases meet criteria for
major aphthae (>1 cm). Some patients can further
be classified as having complex aphthosis, because
they have recurrent vulvar ulcers and concurrent
oral ulcers in the absence of other features of BD.
derm.theclinics.com

This work was not supported by a grant or other funding source.

a
Dermpath Diagnostics, 100 Midland Avenue, Port Chester, NY 10573, USA
b
Department of Dermatology, Columbia University, 161 Fort Washington Avenue, 12th Floor, New York City,
NY 10032, USA
E-mail address: gracebandow@gmail.com

Dermatol Clin 28 (2010) 753–763

doi:10.1016/j.det.2010.08.008
0733-8635/10/$ e see front matter Ó 2010 Elsevier Inc. All rights reserved.
754 Bandow

In the case of vulvar aphthae, keratinized, hair-

bearing, as well as mucosal skin can be involved.
Reported sites include the vagina, introitus, for-
chette, labia minora, labia majora, and perineal
body. The most common location is the medial
aspect of the labia minora, often presenting bilat-
erally on opposing labial surfaces as “kissing aph-
thae” (Figs. 1 and 2).7,8 Ulcers are typically 1 to 2
mm deep with well-demarcated, ragged borders.
Borders can become overhanging and heaped
up, sometimes simulating an ulcerated malignant
tumor. The base of the ulcer ranges from black,
necrotic tissue, to gray or yellow adherent
exudates. The surrounding skin is usually erythem-
atous, edematous, warm, and tender. Associated
regional lymphadenopathy and cellulitis can
occur.
As with the oral variant, the cause of vulvar aph-
thae is not known and even less well studied. They
can occur in adult women, but are more common
in adolescent or premenarchal girls who are
neither sexually active/abused, nor immunocom-
promised. Their discovery can be alarming and
often precipitates an anxiety-provoking, costly,
and unsuccessful search for sexual abuse or sexu-
ally transmitted infections. Patients and even
many clinicians do not recognize noninfectious
causes of vulvar ulcers; education about this entity
is essential. Fig. 2. Vulvar aphthous ulcer in a woman.
Lipschutz first reported vulvar aphthae in 1913 in
adolescent girls in whom no specific cause was
identified.9 Many authors have questioned the reports describe isolation of EBV directly from
association with a viral infection, based on the base of the ulcer either by culture or by poly-
frequently associated antecedent fever, myalgias, merase chain reaction (PCR).8,10,11
and malaise. Epstein-Barr virus (EBV) has been Various theories have been postulated to
most commonly implicated. Halvorsen and explain the development of vulvar ulcers associ-
colleagues identified and reviewed 26 individual ated with EBV. EBV is a ubiquitous virus, and
case reports of EBV-associated aphthae, a diag- both the oropharynx and genital tract have been
nosis which was supported by initial and convales- shown to harbor EBV even in the absence of
cent antibody titers and Monospot testing.10 Few symptoms.12 Therefore, direct transmission from
sexual partners, either by genitalegenital or oro-
genital contact, has been suggested as the
cause.13 Many of the reported cases, however,
occurred in patients before the onset of any kind
of sexual activity. Of 26 reported cases, only 6 re-
ported prior sexual activity.10 It has been postu-
lated, based on these cases, that either
autoinoculation or hematogenous spread from
the patient’s own oropharyngeal infection is the
source for these vulvar lesions.8,14,15
Efforts to prove an association with specific
viruses or other infections in larger cohorts have
failed to confirm this theory. In a retrospective
review of nine patients with nonsexually trans-
mitted vulvar ulcers, eight of whom were preme-
narchal, none had evidence for EBV infection.16
Fig. 1. Vulvar aphthous ulcer in a teenage girl. In a larger review 2 years later, Huppert and
 Diagnosis and Management of Vulvar Ulcers
colleagues7 studied 20 patients with vulvar aph-
thae, 5 of whom were premenarchal. Although 7
out of 20 patients appeared ill on initial examina-
tion, and 19 out of 20 had systemic complaints
compatible with a viral illness (the most common
being fever, malaise, and headache); only 2 had
acute EBV and 2 had possible (equivocal) cyto-
megalovirus (CMV) infections. A thorough search
for bacterial and fungal infections was negative in
all study participants.
Other viruses have been implicated in vulvar
aphthae. One author reported the case of a 13-
year-old girl with influenza A and concomitant
major vulvar aphthae. However, the patient had
a recurrence of the lesions 2 months after the initial
infection without a systemic viral illness.17 There is
one report of a large ulcer of the labium minus
associated with typhoid fever (Salmonella paraty-
phi) in a 25-year-old woman with a recent travel
history.18 Most likely, many different viral infec-
tions, either respiratory or gastrointestinal, can
precipitate vulvar aphthae, making a specific
search extremely difficult.
Noninfectious causes have also been sought to
explain vulvar aphthae in young girls. Friction and
occlusion from tight-fitting clothing has been
proposed as a physical cause in this group. Cebesoy
and colleagues19 noted that 10 out of 10 premenar-
chal girls between the ages of 9 and 13 with vulvar
aphthae associated with no known cause or
underlying systemic illness reported frequently
wearing tight-fitting pants or polyester underwear.
Seven out of 10 had kissing ulcers, and authors
proposed that chronic irritation was possibly playing
a role.
Evaluation of Vulvar Aphthae
The most important aspect of the evaluation of
a patient with vulvar aphthae is a complete history
and physical examination, with particular attention
to signs or symptoms of an underlying associated
systemic condition: BD human immunodeficiency
virus (HIV), malabsorption, ulcerative colitis,
Crohn’s disease (CD), celiac disease, cyclic neu-
tropenia, periodic fever syndromes, and leukemia.
Regardless of the debate over a true association
with a recent viral infection, signs and symptoms
such as fever, malaise, myalgias, upper respiratory
disease, and gastrointestinal symptoms should be
elicited. Questions pertaining to triggering factors
or exposures such as trauma, abuse, and sexually
transmitted infections should be posed carefully.
Excluding BD becomes important in patients
who have recurrent oral and vulvar ulcers, and
may not be possible on the first episode. This is
discussed in greater detail. Obtaining a detailed
755
history may not reveal an underlying etiology,
and this should not discourage the patient or
physician. Patients and parents should be reas-
sured that vulvar aphthae are similar to oral aph-
thae in that a cause is often not identified.
An extensive laboratory work-up is often under-
taken, creating great anxiety on the part of the
patient and parents, and generating enormous,
unnecessary medical expense. These searches
are usually futile and should be tailored to the
history and examination. Excluding HSV with viral
culture or PCR is prudent. In sexually active or
high-risk patients, screening for syphilis and HIV
is appropriate. LGV, GI and chancroid are rare in
the United States and should only be pursued in
cases with a high index of suspicion. Based on
current literature, search for EBV and CMV is not
recommended. Routine bacterial and fungal
cultures reveal skin flora or nonpathogenic
bacteria and do not add benefit.
Obtaining a biopsy may be difficult, particularly
in a young patient. Results are typically nonspe-
cific: chronic active inflammation and necrosis
without vasculitis.15,20 If a biopsy is performed,
care should be taken to obtain a full-thickness
punch or incisional specimen that includes skin
from the periphery of the ulcer, rather than from
the center of the lesion. In a high-risk patient in
whom infection is suspected, biopsy with special
staining for organisms can be a helpful way to
make the diagnosis.
Chronic or recurrent vulvar aphthae in the
absence of HIV, cyclic neutropenia, inflammatory
bowel disease, or BD (primary complex aphthosis)
is rare. Therefore, search for an underlying cause
(secondary complex aphthosis) should be thor-
ough. Continuous management to assess for the
evolution for BD is essential, since patients may
initially present with vulvar aphthae, and later
meet criteria for BD. Similar to the evaluation for
primary, isolated episode of vulvar aphthae,
history and physical examination are the most
important components of a work-up for chronic
or recurrent aphthae.
Laboratory evaluation of chronic vulvar aphthae
should include HSV PCR or culture and HIV
testing. Neutropenia and hematologic deficiencies
should be ruled out with a complete blood count
with differential, serum iron, folate, zinc, and
vitamin B12.1 Consider searching for celiac with
antibody testing and HLA-B27 for BD.21,22
Treatment of Vulvar Aphthae
Many treatments for oral aphthae have not been
rigorously studied and for vulvar aphthae have
not been studied at all. Therefore, treatment of
756 Bandow
vulvar aphthae is based on that of oral aphthae,
case reports, and mostly anecdotal experience.
National registries and randomized trials are
needed to assess the benefit of various treatment
modalities.
The main components of treatment are
supportive care, including adequate pain manage-
ment, and the reduction of ulcer duration. Treat-
ment of recurrent or chronic ulcers is directed at
resolution and prevention.
Supportive care begins with patient and parent
reassurance that aphthae are not infectious,
communicable, or sexually transmitted. Making
the comparison with more commonly known
“canker sores” can be helpful. Rest and proper
fluid and nutrition are recommended, especially
in the setting of systemic symptoms. Twice daily
sitz baths in plain, warm water are the best method
for gentle cleansing. Cleansing with a hand-held
shower head is a good alternative. Soaps and
other topical over-the-counter agents are not
tolerated and should be discouraged because of
their irritant or allergic potential.
Pain can be severe and must be addressed
adequately. Barrier agents are helpful in managing
painful ulcers. Orabase (carmellose sodium) is
a denture adhesive paste that provides a barrier.
It can be used either alone or compounded with
a topical corticosteroid.
Developed in the 1980s, sucralfate is a basic
aluminum salt of sucrose octasulfate, which binds
preferentially to proteins on ulcerated tissue and
promotes healing by multiple different mecha-
nisms. It has antibacterial properties,23,24 stimu-
lates fibroblast and keratinocyte proliferation,25
and promotes angiogenesis.26 Sucralfate has
been extensively studied for use in disease of the
gastrointestinal tract, mostly peptic ulcer disease.
Given its success in this area, clinicians have
adopted it for treating a myriad of other erosive
and ulcerative conditions including burns,27
chronic venous ulcers,28 and severe adult erosive
diaper dermatitis.29 There is one published report
of its successful use in three patients with vaginal
ulcerations caused by pessary use, laser ablation,
and an ulcer of unknown etiology.30 These patients
were treated with sucralfate 10% suspension
douches twice daily and experienced complete
resolution of long-standing ulcers that had been
refractory to previous treatments. Similar to Ora-
base, sucralfate also can be compounded with
a topical steroid.
Polyvinylpyrrolidoneesodium hyaluronate gel
(Gelclair) is a viscous oral gel with two barrier-
forming ingredients that adhere to mucosal
surface. It is a class 1 medical device approved in
2001. Since that time, multiple studies have shown
its efficacy in relieving pain secondary to oral mu-
cositis from chemotherapy.31 One open trial of 30
patients, including 4 with severe diffuse aphthae
of unknown cause and 10 with severe acquired
immunodeficiency syndrome (AIDS)-associated
oral lesions noted significant reduction in pain
scores at 5 to 7 hours and at 1 week after use.32
This is a novel and interesting agent that could
also be evaluated for pain control in vulvar ulcers.
Topical anesthesia is the second important
component of pain management, and can be
delivered in a number of formulations. Various
compounded topical “caine” anesthetics are
effective. Lidocaine can be dispensed to the
patient for use at home up to four times daily in
various preparations and vehicles: 2% gel, spray,
or viscous solution; 4% cream; or 5% ointment.
Gel or ointment is preferred. Huppert describes
success with benzocaine 20% oral gel.7
External dysuria can be severe. Voiding under
water in a bathtub and use of topical anesthetics
and barrier agents before micturition are helpful
solutions.
Pain can be managed with nonsteroidal anti-
inflammatory drugs or oral narcotic agents.
Some patients, particularly young girls, may
require short hospitalization for effective pain
management, placement of a Foley catheter,
rest, and wound care. Patients who appear to
have secondary cellulitis of surrounding tissue
warrant antibiotics.
While the immunopathogenesis of aphthae is
poorly understood, medical treatment is directed
at diminishing inflammation. Of the topical agents
available, a potent inhibitor of inflammatory medi-
ators, amlexanox 5% oral paste (Aphthasol), is the
most extensively studied. For oral aphthae, it is
superior to both placebo paste and to no treat-
ment at all for reduction of pain, ulcer size, and
ulcer duration.33 Additional benefit can be ob-
tained by starting the paste at the onset of
prodromal symptoms rather than waiting for active
ulceration.34 Using this method, Murray and
colleagues found that only 35% of patients who
treated mucosa with prodromal symptoms went
on to develop an ulcer, and healing time was 4.1
days faster in those who did develop an ulcer. Effi-
cacy of amlexanox paste is equal to clobetasol
ointment for the treatment of oral aphthae.35 Am-
lexanox is another agent that should be evaluated
for use in vulvar aphthae.
The mainstay of topical therapy for vulvar
aphthae is corticosteroids. Double-blind, placebo-
controlled trials showed that topical corticoste-
roids significantly reduce oral ulcer duration and
pain when compared with placebo.36,37 Class 1
topical steroids should be used in their ointment
 Diagnosis and Management of Vulvar Ulcers
form to reduce exposure to irritant or allergic
components of creams, gels, or foams. Physicians
should not hesitate to use ultrapotent steroids on
the vulva in this circumstance, presuming the
patient or parent understands appropriate focal
application. Although lacking supportive data
both for oral and vulvar aphthae, intralesional
and oral steroids also may have benefit, and
studies are needed to assess their use over
current topical agents.
Tetracycline antibiotics have been used in
various formulations for treating oral aph-
thae.38,39 In trials, the mouthwashes are dosed
four times daily for 1 to 2 minutes. They signifi-
cantly reduce pain and duration of recurrent
ulcers compared with placebo. Formulas for
compounding mouthwashes have been
described.40 Use of topical antibiotics for vulvar
ulcers has not been studied; however, many
case reports describe using oral antibiotics for
presumed infection during management of acute
vulvar aphthae. The failure of antiseptic mouth-
washes41,42 to improve pain or ulcer duration
for oral aphthae suggests that the antimicrobial
effect is not as important as perhaps the anti-
inflammatory effect of these antibiotics. Trials
exploring the use of either oral or topically
applied antibiotics for vulvar ulcers are
warranted.
Treatment of Chronic/Recurrent Aphthae
Chronic vulvar aphthae unassociated with an
underlying illness (primary complex aphthosis) is
rare, and studies to support therapeutic decisions
do not exist. Physicians who manage these
patients must extrapolate from experience in the
treatment of chronic oral aphthae. Because the
mechanism of ulcer formation is likely similar in
these two anatomic sites and can occur simulta-
neously in the same patient, the data on treatment
of chronic oral aphthae are reviewed here.
The approach to managing complex aphthosis is
different from managing a solitary episode or
simple aphthae. Complex aphthosis, by definition,
is chronic and recurrent, thus requiring systemic
agents to heal long-standing lesions, reduce recur-
rences, and induce remission. The main systemic
agents used include thalidomide, dapsone, colchi-
cine, pentoxifylline, and tumor necrosis factor (TNF)
inhibitors. Treatment choice is based on patient
profile, medical history, and previous treatment
trials. As with any chronic dermatologic condition
requiring ongoing systemic therapy, rotating
agents to reduce adverse effects is helpful.
Comparisons of systemic therapeutic modalities
for chronic aphthae are rare. Letsinger and
757
colleagues published one of the first reports of
a large series of this kind. This paper reviewed
treatment of 42 patients with primary complex
oral aphthosis. The authors proposed a therapeutic
strategy starting with colchicine 0.6 mg two to
three times daily as tolerated, progressing to
dapsone dosed from 25 to 100 mg daily, and
then to a combination of these two agents at full
tolerated doses. The authors found that the two
drugs combined were much more effective than
either one alone, and nearly as effective as thalid-
omide, the final step in their suggested therapeutic
ladder. Fifty-seven percent and 59% of patients
achieved at least 50% improvement in these last
two treatment groups, respectively.
Since the publication of this study, a second
review of systemic treatments for 21 patients
with severe recurrent oral aphthae has been pub-
lished.20 Patients initially were treated with predni-
sone for 2 weeks starting at 0.5 mg/kg/d, which
was reduced to half that dose for a second
week. Simultaneously, one of four systemic agents
was started and maintained for 6 months: thalido-
mide, dapsone, colchicine, or pentoxifylline. The
authors found that thalidomide was the most effi-
cient and best-tolerated drug, with seven out of
eight (87.5%) patients experiencing complete
remission. Eight of nine patients treated with
dapsone (89%) and eight of nine patients treated
with colchicine (89%) experienced excellent-to-
moderate improvement in their disease. Three
out of five (60%) patients treated with Pentoxifyl-
line had excellent-to-moderate improvement.
Dapsone was best for inducing remission, with
three patients remaining ulcer free for up to 9
months after discontinuation of the drug. Other-
wise, most patients relapsed within weeks to
several months of cessation of therapy.
Introduced in the 1950s as a sedative, thalido-
mide was subsequently banned worldwide in
1962 after the discovery of its devastating terato-
genic effects. Thalidomide saw a renewed accep-
tance for its use in erythema nodosum leprosum
(ENL) and was approved and classified as an
orphan drug for this indication by the US Food
and Drug Administration in 1998.43 ENL remains
the only approved indication for this drug;
however, it has re-emerged as an alternative
off-label therapy for many other dermatologic
conditions.44 Careful monitoring using the System
for Thalidomide Education and Prescribing Safety
(STEPS) program is mandatory to ensure appro-
priate use and prevent pregnancy. The mecha-
nism of action of thalidomide is multifactorial and
poorly understood, but in the case of aphthae, is
probably mediated in part by its anti-TNF
effect.45,46
758 Bandow
Its effectiveness in complex aphthosis initially
was shown in three open-label trials using thalido-
mide doses ranging from 100e400 mg/d. Most
patients had significant improvement or complete
resolution of lesions and pain within several weeks
of starting therapy.47e49 Larger randomized trials
definitively established the efficacy of this drug.
On 100 mg/d, 48% and 44% of patients experi-
enced complete remission compared with only
9% and 8% of patients receiving placebo.50,51
These studies reported relapse times of 20 to 30
days after stopping therapy.
Successful use of TNF inhibitors in BD has led to
their off-label use in complex aphthosis. Schein-
berg reported success using etanercept for two
patients with chronic recurrent aphthous stoma-
titis, one meeting criteria for BD.52 Both patients
discontinued thalidomide, despite its effective-
ness, because of adverse effects, and were
subsequently treated with etanercept. Complete
remission occured in both patients within 3 and 5
weeks of therapy. Recurrence was noted after
discontinuation within 5 and 7 weeks. Each patient
quickly responded after a second reintroduction of
etanercept. Robinson and colleagues subse-
quently reported success using etanercept for
another case of severe, recalcitrant oral aph-
thae.53 Treatment with adalimumab led to
complete resolution of a 7-year history of recalci-
trant, severe major aphthae in an 18-year-old.54
Such encouraging reports are increasing in
number, and larger trials using these agents are
desperately needed for this disabling condition.
Behçet’s Disease
BD is a multisystem disease of unknown etiology,
with the highest prevalence in the Mediterranean,
particularly Turkey, with a rate of 1 case per 250
people in the population over 12 years old.55 A
pathognomonic test for BD does not exist; there-
fore the diagnosis is made based on the satisfac-
tion of established criteria. International study
group criteria for BD were established in 1990.56
By this consensus, patients must have recurrent
oral aphthae at least three times in 1 year, plus
two of the following:
Recurrent genital aphthae
Uveitis or retinal vasculitis
Erythema nodosum-like lesions or papulo-
pustular skin lesions
Positive pathergy test.
Ulcers involving oral and genital skin and
mucosa are a hallmark of the disease. Second to
oral ulcers, genital ulcers are the next most
common feature of BD, occurring in 57% to 93%
of patients.57 Recognizing these lesions is essen-
tial, because they may precede other features of
the disease. Overlooking this association may
result in delay in diagnosis and an increase in
mortality.58 Aphthae associated with BD typically
occur more frequently and more often in crops
compared with recurrent aphthous stomatitis
(RAS).59 Genital ulcers of BD typically start as
a tender nodule, become deep and painful, and
eventually heal with scarring. Searching for scars
on genital skin, even in the absence of active, clin-
ical disease, is an important part of the examina-
tion.58 Ulcers typically are found on the labia
majora, but can occur anywhere on the vulva, peri-
neum, or perianal skin. They can also occur intra-
vaginally, potentially leading to fistula formation
with the urethra or bladder.58 Exceptionally deep
external genital ulcers can lead to labial
destruction.58
Treatment of aphthae of BD is based on experi-
ence in treating RAS and has been reviewed in
detail elsewhere.59 In the opinion of Alpsoy, who
has written extensively about this disease, colchi-
cine alone or plus benzathine penicillin is a good
starting point for women with genital ulcers.
Thalidomide and dapsone are second choices
with immunosuppressive agents (cyclosporine,
azathioprine, and TNF inhibitors) to follow for unre-
sponsive patients. Topical barriers, antibiotics,
anesthetics, and corticosteroids can be used as
described for treating primary aphthosis.
TNF-alpha, derived from gammaedelta Th-1
lymphocytes, is postulated to play a role in the
pathogenesis of BD. Accordingly, off-label use of
TNF inhibitors is increasingly being used for
BD.60,61 Although primarily used for ophthalmic,
gastrointestinal, and other more severe systemic
manifestations, there are multiple reports of
successful use of TNF inhibitors, particularly inflix-
imab, for treating severe oral and genital aphthae
of BD.62e66 Complete remission is observed with
maintenance therapy. A representative case is
illustrated by Robertson and colleagues, who
successfully used infliximab to treat severe oro-
genital aphthae associated with BD. The patient
was a 65-year-old woman who had failed treat-
ment with dapsone, thalidomide, azathioprine,
cyclosporine, and colchicine. There was marked
improvement after the first infusion with infliximab
(scheduled at 0, 2, and 6 weeks at 5 mg/kg). By the
third infusion, she was completely clear of ulcera-
tions for the first time in 10 years.64
Likewise, etanercept has shown to be useful for
treating aphthae of BD. Two female patients en-
joyed complete remission of oral and vulvar ulcers
when etanercept, 25 mg twice weekly, was added
to their regimens of methotrexate in one case and
 Diagnosis and Management of Vulvar Ulcers 759

methotrexate and prednisolone in the second.67,68

Other data indicate that etanercept may be best
reserved for clearing oral aphthae rather than
genital aphthae. A recent randomized controlled
trial comparing 25 mg twice weekly etanercept
with placebo for mucocutaneous BD in 40 men
showed that the drug had little effect on genital
ulcers, while oral ulcers began clearing within 1
week of treatment.69
Infliximab was effective in a case resistant to
etanercept.70 This is most likely due to the effect
of infliximab on both soluble and membrane-
bound TNF, and therefore, more powerful TNF
blockade. With this in mind, a reasonable
approach is to treat patients with etanercept as
a first-line agent, due to its excellent safety profile,
and move to infliximab if response is suboptimal.

HIV-Associated Aphthous Ulcers

Most studies examining HIV-associated ulcers are
conducted in Africa and involve the risk of trans-
mission and coinfection with herpes simplex,
syphilis, or chancroid. The literature investigating
vulvar aphthae associated with HIV is scant, con-
sisting primarily of case reports. HIV-associated
aphthae are similar to ulcers that affect the oral
mucosa, esophagus, and rectum in these patients,
and pathogenesis may be the same.
They are typically large, painful, and recurrent
(Fig. 3). Patients are generally severely immuno-
compromised with a low CD4 count and AIDS-
defining infections.71 Thirty-seven percent have
coexistent oral ulcers.71 HIV-associated aphthae
can persist for weeks or months, becoming
necrotic and causing disabling pain. Local
destruction by nonhealing ulcers can be severe,
with formation of a recto-vaginal fistula reported
in one woman and a labialevaginal fistula extend-
ing to the ischiorectal fossa in another.72,73 Five
fistulas resulting from HIV-associated aphthae
were reported in a national survey involving 29
severely immunocompromised women: four
recto-vaginal fistulas requiring diverting colosto-
mies and one vaginaleperineal fistula.71
The pathogenesis of HIV-associated aphthae
remains unknown. Immunosuppression, altered
host response, and direct infection by HIV are
proposed etiologies. In support of these theories
is the fact that the CD4 count is typically low,
and some women respond to antiretroviral
therapy.71,74 In one retrospective review of 307
HIV-positive women, 14% were found to have
vulvar ulcers, 60% of which were classified as
aphthae of unknown etiology. By definition, neither
malignant nor ulcer-causing infections was identi-
fied on work-up of these patients.73
Fig. 3. Large, destructive genital ulcer associated with
HIV.
Although biopsies are usually nondiagnostic,
obtaining one as part of the evaluation is neverthe-
less recommended in patients with HIV-
associated aphthae both to rule out malignancy
and as a method of searching for potentially treat-
able infectious causes such as CMV, HSV, and
mycobacterial infections. All women presenting
with HIV-associated ulcers should additionally be
screened for HSV and syphilis. Screening for
chancroid, LGV, and GI in select patients with
high-risk behavior or from endemic regions is
also prudent.
Early identification and treatment of HIV-
associated vulvar aphthae are essential given the
potentially crippling sequelae. Variably favorable
response typically is seen with either topical, intra-
lesional, or oral corticosteroids.71 High-dose corti-
costeroids are reported to promote healing of
individual patients,72 although the ideal dosing
regimen has not been studied. Antiviral therapy
with acyclovir is not beneficial.71 Given the
successful use of thalidomide for the treatment
of complex aphthosis and aphthae of BD, this
drug has been used to treat HIV-associated ulcers.
The largest trial is a randomized controlled trial of
57 HIV-positive patients with oral aphthae. The
treatment group received 200 mg/d. After 4 weeks
of treatment, 55% of these patients had complete
healing of ulcers compared with only 7% of the
placebo group.75
760 Bandow

Crohn’s Disease transmitted infections such as granuloma ingui-

nale. The ulcerations and occasionally the pres-
CD is an inflammatory bowel disease character-
ence of vasculitis histologically can help
ized by noncaseating granulomatous lesions,
differentiate CD from sarcoidosis. Polarizing
occurring in a skip pattern at any location along
microscopy should be performed in search of
the gastrointestinal tract from the mouth to the
foreign body material. Tuberculin skin test, chest
anus. Mucocutaneous manifestations occur in up
radiograph, tissue culture, PCR, and special stains
to 44% of patients,76 but they do not necessarily
can help identify mycobacterial and deep fungal
mirror intestinal involvement.77 Skin manifesta-
infections. Classic HS usually can be distinguished
tions can be categorized as either histologically
based on clinical appearance alone; however,
specific or nonspecific (reactive). Histologically
differentiation from CD can be difficult. Clinical
specific lesions have noncaseating granulomas
features of abscesses, fistulae, webbed scars,
similar to those seen in the intestinal lesions.
and comedomes involving skin along the milk line
Nonspecific or reactive skin manifestations
in a recurrent nature are typical of HS. The presence
include entities such as pyoderma gangrenosum,
or history of other follicular occlusive entities adds
erythema nodosum, and oral aphthae.76
support to the diagnosis: severe cystic acne, piloni-
Of those who present with cutaneous CD, 70%
dal cyst, and dissecting cellulitis of the scalp.
present with genital involvement.78 Therefore, CD
Treatment of CD requires systemic administra-
initially may present to the dermatologist in the
tion of various antibiotics, immunosuppressive
form of vulvar ulcerations, and recognition of these
agents, and anti-inflammatory agents such as
findings should prompt an investigation for the
metronidazole, corticosteroids, azathioprine, sul-
disease.
fasalazine, or 6-mercaptopurine. Cutaneous CD
Vulvar CD presents most commonly with
is rare, and treatment trials have not been per-
erythema and unilateral or bilateral labial swelling.
formed. A small series showed that infliximab is
Chronic edema leads to firm coalescing papules
very effective in healing pyoderma gangrenosum
and fibrotic nodules, which could be confused
and aphthous stomatitis associated with CD.79 In-
with lymphatic obstruction.5 Ulcers associated
fliximab and adalimumab have both been used
with CD are classically long “knife cut” lesions in
successfully to treat individual cases of cutaneous
the genitocrural folds or interlabial creases. This
CD.80e82 Cyclosporine and mycophenolate mofetil
presentation is almost pathognomonic for CD
have been reported to be successful in individual
(Fig. 4). Other genital findings are skin tags,
cases of cutaneous CD.83,84 Other cutaneous
abscesses, draining fistulas, and eventually scar-
directed therapy includes intralesional corticoste-
ring.78 Perianal fistulae form by direct extension
roids, incision and drainage for abscesses, and
of rectal CD, and can extend to the vagina or vulva.
surgical repair for fistulae.5
Histologic findings of noncaseating granulomas
help establish the diagnosis. The differential diag-
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